Department of Biological Science and Technology, National University of Tainan, Tainan, Taiwan.
Arch Pharm Res. 2012 Jan;35(1):119-27. doi: 10.1007/s12272-012-0113-z. Epub 2012 Feb 2.
The histamine receptor H1 antagonist homochlorcyclizine (HC) has been widely used as an antihistamine agent for the treatment of allergies. However, the effect of HC on skin pigmentation is not known. In the present study, we investigated the inhibitory effect of HC on melanogenesis in mouse B16 melanoma cells. Our results showed that HC inhibited melanogenesis in either α-melanocyte stimulating hormone (α-MSH)- or 3-isobutyl-1-methylxanthin (IBMX)-stimulated B16 cells in a dose-dependent manner. Despite the strong inhibition of melanogenesis by HC, it was surprisingly found that HC did not reduce either cellular or melanosomal tyrosinase activity in α-MSH-stimulated B16 cells. In addition, HC also did not directly inhibit either murine or mushroom tyrosinase activity in the cell-free system. Moreover, western blotting and reverse-transcription polymerase chain reaction (RT-PCR) analyses respectively confirmed that HC did not downregulate levels of tyrosinase protein and its mRNA in α-MSH-stimulated B16 cells. These results clearly demonstrated that HC inhibits melanogenesis of B16 cells by a mechanism other than reduction of the cellular tyrosinase activity. From the present study, HC was proven to be a good candidate as a skin-whitening agent for treatment of skin hyperpigmentation, and this generic drug might be suitable for use in combination with other depigmenting agents due to its unique inhibition mechanism.
组胺受体 H1 拮抗剂盐酸环嗪（HC）被广泛用作治疗过敏的抗组胺药。然而，HC 对皮肤色素沉着的影响尚不清楚。在本研究中，我们研究了 HC 对小鼠 B16 黑色素瘤细胞中黑色素生成的抑制作用。结果表明，HC 以剂量依赖的方式抑制 α-促黑素细胞激素（α-MSH）或 3-异丁基-1-甲基黄嘌呤（IBMX）刺激的 B16 细胞中的黑色素生成。尽管 HC 强烈抑制黑色素生成，但令人惊讶的是，HC 并没有降低 α-MSH 刺激的 B16 细胞中的细胞或黑素小体酪氨酸酶活性。此外，HC 在无细胞体系中也不能直接抑制鼠或蘑菇酪氨酸酶的活性。此外，Western blot 和逆转录聚合酶链反应（RT-PCR）分析分别证实，HC 没有下调 α-MSH 刺激的 B16 细胞中酪氨酸酶蛋白及其 mRNA 的水平。这些结果清楚地表明，HC 通过一种不同于降低细胞酪氨酸酶活性的机制抑制 B16 细胞的黑色素生成。本研究证明，HC 是一种治疗皮肤色素沉着过度的皮肤增白剂的候选药物，由于其独特的抑制机制，这种非专利药物可能适合与其他脱色剂联合使用。
